The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration
The analgesia effect of duloxetine on post-operative pain via intrathecal or intraperitoneal administration
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度洛西汀鞘内或腹腔给药对术后疼痛的镇痛效果
DOI：
10.1016/j.neulet.2014.03.046
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发表时间：
2014-05-07
影响因子：
2.5
通讯作者：
Dong, Yu-Lin
中科院分区：
文献类型：
--
作者：
Sun, Yong-Hai;Li, Hong-Shi;Dong, Yu-Lin
预防慢性术后疼痛 (POP) 的一种有前景的策略是在早期阶段通过副作用较少的有效药物来减轻急性 POP。度洛西汀是血清素 (5-HT)-去甲肾上腺素 (NE) 再摄取抑制剂 (SNRI) 的一种，用于治疗多种急性和慢性疼痛。然而，其对 POP 的影响尚未得到研究。在本研究中，我们使用 POP 大鼠模型研究了度洛西汀的抗过敏作用。还通过使用5-HT2A（酮色林）或α2-去甲肾上腺素受体（咪唑克生）拮抗剂评估了脊髓5HT（2A）和α2-去甲肾上腺素受体可能的参与。最后，通过体内微透析的方法，研究了腹膜内（i.p.）递送度洛西汀后脊髓NA和5-HT水平的增加。结果表明，鞘内 (i.t.) 或腹膜内注射 (i.p.)度洛西汀的递送以剂量依赖性方式产生抗痛觉过敏作用。度洛西汀的抗过敏作用因酮色林或伊达佐生预处理而部分减弱。微透析研究表明，脊髓背角的 5-HT 和 NA 浓度增加，在腹腔注射后 30 分钟达到峰值。注射20mg/kg度洛西汀。这些发现表明度洛西汀通过增加脊髓 NA 和 5-HT 水平以及激活脊髓 5-HT2A 或 α2-去甲肾上腺素能受体来抑制 POP。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
One promising strategy to prevent the chronicity of post-operative pain (POP) is to attenuate acute POP during the early phase by efficacious medications with fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic pain. However, its effect on POP has not been investigated. In the present study, we investigated the anti-hypersensitivity effect of duloxetine using a rat model of POP. The possible involvement of spinal 5HT(2A) and alpha 2-noradrenergic receptors were also evaluated by using antagonists for 5-HT2A (ketanserin) or a2-noradrenergic receptors (idazoxan). Finally, with the method of in vivo microdialysis, the increase in spinal NA and 5-HT levels after intraperitoneal (i.p.) delivery of duloxetine were investigated. The results showed that intrathecal (i.t.) or i.p. delivery of duloxetine produced an anti-hyperalgesic effect in a dosedependent manner. The anti-hypersensitivity effect of duloxetine was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30 min after i.p. injection of 20 mg/kg duloxetine. These findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT levels and activating spinal 5-HT2A or a2-noradrenergic receptors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.